Defining the underpinnings of Neuropeptide Y (NPY)'s control of hunger and body fat

More than 60% of people in the UK are overweight or obese. The primary cause of excess body weight is the consumption of more food than the body requires, calories that are then stored in fat. The reason this is important is because poor diet and excess body fat commonly has a detrimental impact on health. The focus of this application is clarifying the biology behind food choice (why do we prefer cake to cabbage?), meal size and body fat accumulation. The brain represents the master coordinator of appetite, employing discrete interwoven circuits to continually appraise and respond to changes in energy availability. A principal node within this network is a brain chemical called brain Neuropeptide Y (Npy), which is a powerful hunger hormone. Therefore, a clear understanding of the precise mechanism through which Npy modulates how much food we eat and the types of food we choose is of intense interest. However, discoveries in this direction have been hindered by a lack of precise tools. Recent technological advances now provide a means to overcome this obstacle, affording a way to discover the location of crucial sources of the brain's Npy that influence our decisions about what foods we choose to eat and whether these calories are used or stored in body fat. We think that Npy within a brain region called the nucleus of the solitary tract performs this essential function. We believe Npy in this region does two things to make sure that we have enough calories on board. One, it increases hunger, food intake and a preference for high calorie foods. And two, it tells the body to store calories in fat so that we have a supply of energy later if we need it. Data generated thus far support this idea. Using a combination of state of the art techniques, we will test the function of this special source of Npy in hunger and body fat in the proposed research programme. This work is important because we believe we have found an essential way that the brain controls hunger and food choice. Moreover, we think we have uncovered a new way that the brain talks directly to body fat, telling it to either store or expend calories. We anticipate that these studies will provide fundamental insight into the biological underpinnings of appetite, food choice, body weight and body fat, findings relevant to the prevention and treatment of obesity.